葛根素通过调节TLR4-MyD88-NF-κB信号通路对糖尿病小鼠肾损伤的改善作用  

Puerarin improving renal injury of diabetic mice by regulating TLR4-MyD88-NF-κB signaling pathway

作　　者：尧献赏 邓旺生 徐小惠 张晓琳[1] 吴娅妮 庞小红 黄建春[1] 卢顺玉 Yao Xianshang;Deng Wangsheng;Xu Xiaohui;Zhang Xiaolin;Wu Yani;Pang Xiaohong;Huang Jianchun;Lu Shunyu(College of Pharmacy,Guangxi Medical University,Nanning 530021,China;The People’s Hospital of Longhua,Shenzhen 518109,China;Guangxi Medical University Cancer Hospital,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,南宁530021 [2]深圳市龙华区人民医院,深圳518109 [3]广西医科大学附属肿瘤医院,南宁530021

出　　处：《广西医科大学学报》2023年第11期1771-1777,共7页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82104558);广西医科大学附属肿瘤医院青年科学基金资助项目〔No.院青2021-04号(院内)〕;广西自然科学基金资助项目(No.2023GXNSFBA026153)。

摘　　要：目的:研究葛根素(puerarin)通过调节TLR4-MyD88-NF-κB信号通路对糖尿病小鼠肾损伤的改善作用。方法:小鼠腹腔注射链脲佐菌素(STZ)构建糖尿病小鼠模型,分为糖尿病模型组(模型组)、二甲双胍组、葛根素组,另设正常对照组。正常对照组和模型组小鼠灌胃予生理盐水,二甲双胍组灌胃予二甲双胍320 mg/kg·d^(-1),葛根素组腹腔注射葛根素65 mg/kg·d^(-1),各实验组共干预4周。每周测定各组小鼠的空腹血糖(FBG),称量体重,酶联免疫吸附试验(ELISA)测定各组小鼠血清肌酐、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α),苏木精—伊红(HE)染色观察小鼠肾组织病理损伤情况,免疫组化观察Toll样受体-4(TLR4)、髓样分化因子88(MyD88)、核因子κB(NF-κB)蛋白在肾组织的表达水平。结果:与正常对照组比较,模型组FBG、肌酐、IL-6、TNF-α水平明显升高(P<0.05),肾小球增大,肾组织正常结构被破坏,肾小球基底膜增厚,且肾组织TLR4、MyD88、NF-κB蛋白表达增多(P<0.05);与模型组比较,葛根素组的FBG、Scr、IL-6、TNF-a的含量明显降低(P<0.05),减轻肾组织损伤,肾组织TLR4、MyD88、NF-κB表达减少(P<0.05)。结论:葛根素对糖尿病小鼠肾损伤具有明显的改善作用,可能与其调控TLR4-MyD88-NF-κB信号通路有关。Objective:To investigate the effect of puerarin on renal injury of diabetic mice by regulating TLR4-MyD88-NF-κB signaling pathway.Methods:The diabetic mouse models were established by intraperitoneal injection of streptozotocin(STZ),and were divided into diabetic model group(model group),metformin group as well as puerarin group,and a normal control group was set up.The normal control group and model group were administrated with normal saline,the metformin group was administrated with metformin 320 mg/kg·d^(-1),the puerarin group was intervened with puerarin 65 mg/kg·d^(-1) intraperitoneally,and all experimental groups were treated for 4 weeks.The fasting blood glucose(FBG)and the weight of the mice in each group were measured weekly.Serum creatinine(Scr),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)of the mice were determined by enzyme-linked immunosor-bent assay(ELISA).The pathological changes of renal tissue were observed by hematoxylin and eosin(HE)staining.The expression levels of Toll-like receptor-4(TLR4),myeloid differentiation factor 88(MyD88)and nuclear factorκB(NF-κB)in renal tissue were observed by immunohistochemistry.Results:Compared with the normal control group,the levels of FBG,Scr,IL-6 and TNF-αin the model group were significantly increased(P<0.05),the glomeruli was enlarged,the normal renal tissue structure was destroyed,the basement membrane of glomeruli was thickened,and the expression of TLR4,MyD88 and NF-κB protein in renal tissue was increased(P<0.05).Compared with the model group,the contents of FBG,Scr,IL-6 and TNF-αthe in the puerarin group were significantly decreased(P<0.05),the renal tissue injury was alleviated,and the expression of TLR4,MyD88 and NF-κB in renal tissue was reduced(P<0.05).Conclusion:Puerarin can significantly improve renal injury of diabetic mice,which may be related to the regulation of TLR4-MyD88-NF-κB signaling pathway。

关 键 词：葛根素 糖尿病肾损伤 TLR4-MyD88-NF-κB信号通路 

分 类 号：R285.5[医药卫生—中药学]